The upper respiratory system is commonly defined as the nasopharynx (nose) oropharynx (mouth), laryngopharynx (larynx), trachea and sometimes includes the main stem bronchus and, right and left main stem bronchus. The lower respiratory tract continues through the terminal respiratory bronchioles alveolar ducts and ends with the alveolar sacs. Each progressive branch of the airways results in smaller diameters and shorter length until microscopic in size. Optimally, delivery of inhaled agents to the lower respiratory tract requires shattering a liquid or solid agent into a particle size range of between about 0.2 and 3.0 microns. Penetration of an inhaled agent is defined as the maximum depth that suspended particles can be carried into the respiratory system during a normal inspiratory effort. Deposition of the agent refers to the eventual instability of the particles resulting in a “fall out” on to a nearby surface. Four factors are directly related to the efficiency of deposition of optimal ranged particles: 1) kinetic activity; 2) pattern of respiratory activity; 3) gravity; and 4) inertial impaction. Kinetic Activity is defined as the erratic movement pattern of the medicinal agent irrespective of direction of flow, also known as the Brownian movement. Pattern of Respiratory Activity generally refers to the deposition and retention of inhaled particles which is directly related to inhaled volume and inversely related to ventilatory rate. Gravity refers to the influence of a suspended particle is in direct relation to the particle mass influenced by known and constant gravitational forces which follows Stokes law of Sedimentation. Finally, Inertial Impaction refers to the penetration and deposition of an inhaled agent which includes a strong influence of the theory of inertial impaction. Furthermore, this factor is based on the fact that water particles (and inhaled agents) have a greater mass than gas molecules. In addition, the force moving these particles in a straight line is greater than the force on gas molecules. When a change in direction, as in a splitting bronchiole, the probability of deposition caused by inertial impaction increases as the diameter of the conducting tube airway decreases in size. This is a significant factor in the smaller airways of the lower respiratory tract. Dose dilutions and frequency of inhaled agents has been established based on deposition of the inhaled agent(s) delivered in the optimal size range. Inhaled agents must be stable at a temperature range of 35 degrees Fahrenheit through 130 degrees Fahrenheit.
The unique nebulized features of this product is the ability to not only produce particle of optimal size for traditional inhalation to the lower respiratory tract, but also produces larger particle sizes for deposition into the upper respiratory tract. And, the unique baffling system and jet producing flows can be changed for purposeful alterations in speed of agent delivery (a factor of dilution effecting gravity, inertial impaction, and kinetic activity). Adding these features offers significant expanded utility to include non-traditional inhaled agents to effectively and efficiently be nebulized for targeted penetration and deposition that is not available within a single, mono-purpose nebulizer device. Monitoring the effectiveness of the inhaled agent and adjusting the controllable factors in a “servo-controlled defined protocol” adds an even greater and unique purpose and value to this system.
Many inhaled medications will have a greater safety and efficacy (dose, delivery and frequency) if a narrow window of precise medication can be delivered and cause/effect results can be directly measured, monitored and remotely adjusted. This concept is well understood with parallels seen in high blood pressure management and insulin therapy for diabetics but has not been possible for the delivery of inhaled agents. Furthermore, in some instances it is desirable to deposit agents into the upper respiratory tract, (including the nose and sinuses) transitional airways (trachea and main-stem bronchus) and lower airways for deep lung penetration. A device that included these features will open opportunities to treat traditional respiratory related diseases inflicted upon patients ranging from neonates through geriatrics. In addition, this new delivery and monitoring system provides a new foundation to inhale non-traditional drugs into the lungs such as insulin, antibiotics, pulmonary hypertension drugs, systemic hypertension drugs, hereditary enzyme deficiency replacement agents and neonatal lung-specific treatments. An additional market includes a modified, non-prescription device for naturopathic/homeopathic products. This is very promising as the general consumers in the U.S. and European markets are expanding with diet supplementation, improved vitamin absorption techniques and many new homeopathic treatment alternatives. Inhaling safe agents into the lungs is supported by clinical parameters of a highly vascularized, oxygen enriched and easily accessible delivery route for naturopathic and homeopathic supplements and treatment options.
One of two traditional markets of application includes the category of Chronic Obstructive Pulmonary Disease (COPD) which currently an estimated 16 million people in the United States are diagnosed as having. It is estimated that an additional 14 million or more are still undiagnosed, as they are in the beginning stages and have few or minimal symptoms and have not sought health care yet. COPD is an umbrella term used to describe lung disease associated with airflow obstruction. Most generally, emphysema, chronic bronchitis and chronic asthma either alone or in combinations fall into this category. There is continuing debate as to whether this term also includes Asthma (non chronic), however as a general rule, it is not included as, even though it does have obstructive components to it, it is in part reversible, and is more generally considered a restrictive lung disease.
The second traditional market is asthma. Asthma has been labeled as both a chronic lung and acute disease characterized by inflammation of the airways because of increased sensitivity to a variety of triggers, which can cause narrowing of the airways and breathing difficulty. Asthma affects 14.6 million Americans and increases by about 6% annually. Of that number, 4.8 million are children under the age of 18. Asthma is the number one cause of school absences attributed to a chronic condition. More than 5,400 people in the United States die each year from asthma. Direct and indirect costs of asthma care exceed $6 billion each year. This includes loss of time from work and school, and medical costs. To recover the cost issues, improve the outcomes of therapy and reduce the risks for loss of life, better-nebulized drug delivery and response to therapy monitoring systems will be a required tool before medical scientists and disease management protocols experts deem the disease under better control.
In general, a standard commercial asthma nebulizer is an electromechanical device that requires pressurized air to atomize liquid medication into the form of a very fine aerosol mist for patient inhalation. The pressurized air is generated from an internal portable air compressor with a maximum pressure of between about 30 and 45 psig and is driven by an electrical AC motor that generates a noise level of about 53 dBA. The pressurized air exits the electrical motor and travels through a predetermined length of polyethylene tubing to a patient hand-held medicine chamber. The patient is required to manually measure and fill the medicine chamber (6 cc/ml) with various medications in predetermined amounts as prescribed by the doctor or physician. The medicine chamber is manufactured to specific geometries that determine a nebulization rate of between about 0.15 and 0.3 ml per minute and a flow rate of between about 6 to 8 liters per minute. The medication chamber is pressurized from between about 14 and 25 psig of room air, which contains approximately 21% oxygen and is forced through the medicine chamber. The result of this event is a very fine atomized mist of less than 1 micron particle size product in 80% of the population of medication that a patient inhales. The temperature of the gas inhaled by the patient is between about 80 to 90 degrees Fahrenheit, which is created from friction being generated inside the electrical compressor.
A standard commercial nebulizer has a footprint of about 7.0″ wide×3.8″ high×13.0″ deep (18 cm×10 cm×33 cm) and weighs approximately 7 pounds to 12 pounds and requires an electrical outlet of 115 VAC to operate. The treatment time with this type of device generally takes 10 minutes to 12 minutes to complete. Alternatively, ultrasonic nebulizers are an optional choice for some patients for portability and a have slightly more dispensing resolution in droplet particle size to the patient. However, to be mobile, the patient must hold these heavy units. Thus, the standard commercial asthma nebulizer is extremely large in size, burdensome and complicated to use and not generally practical to use as a portable, interim, self-sufficient device.
Thus, there is a long felt need in the field of chronic and acute respiratory care to provide a medicinal agent delivery system which is light, portable, easy to use and maintain, and is capable of servo-feedback diagnostic monitoring and real-time, physician-initiated, dosage regulation.